Isoastragaloside I inhibits NF-κB activation and inflammatory responses in BV-2 microglial cells stimulated with lipopolysaccharide

The excessive activation of microglia in many neurodegenerative diseases is detrimental to neuronal survival. Isoastragaloside I (ISO I) is a natural saponin molecule found within the roots of Astragalus membranaceus, a famous traditional Chinese medicine. In the present study, the anti-inflammatory effects and the mechanisms of action of ISO I on activated BV-2 cells stimulated with lipopolysaccharide (LPS) were investigated. ISO I dose-dependently inhibited the excessive release of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha in the LPS-stimulated BV-2 cells. Moreover, it decreased the production of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), and mitigated the gene expression of interleukin (IL)-1 beta, TNF-alpha and iNOS induced by LPS. Further experiments revealed that ISO I decreased the phosphorylation levels of nuclear factor-kappa B (NF-kappa B), and suppressed its nuclear translocation and transactivation activity. In addition, it inhibited the activation of signaling pathway molecules, such as PI3K, Akt and mitogen-activated protein kinases (MAPKs). Taken together, our findings suggest that ISO I prevents LPS-induced microglial activation probably by inhibiting the activation of the NF-kappa B via PI3K/Akt and MAPK signaling pathways, indicating its therapeutic potential for neurological diseases relevant to neuroinflammation.